Volume 29, Nº 4 (2025): MEDICAL GENETICS

Relevance. Single-cell RNA sequencing (scRNA-seq) is a modern approach to studying the diversity and heterogeneity of RNA transcripts in individual cells, as well as to identifying the composition of different cell types and functions in organisms, organs, and tissues. Based on NGS (next-generation sequencing), scRNA-seq provides a vast amount of information at high cellular resolution in various fields, enabling new discoveries in understanding the composition and interaction patterns of individual cell types in humans, animal models, and plants. Despite its rapid development, optimization, and automation worldwide over the past 15 years, scRNA-seq remains relatively new and has only recently been used in Russia. The challenge of mastering and successfully implementing this method is urgent and critical - it is a powerful tool for in-depth analysis and diagnostics, as demonstrated by the results of studies in which it has been used. The aim of the review was to examine the basic principles and steps of scRNA-seq implementation, both in terms of technical implementation and sample preparation as an extension of the classic NGS method, as well as in terms of the complexity and expansion of data processing, and the use of new algorithms and databases. We examined commercially available scRNA-seq technologies and technologies described in scientific literature that have served as prototypes and alternatives. We also examined examples and results of the use of such technologies in various fields of science and medicine, such as oncology, senescence, diagnostics, and clinical trials. Conclusion. Development and successful application of the scRNA-seq method in scientific and clinical practice will become the key to a wide range of future discoveries and successful accurate personalized diagnostics and healthcare.

Relevance. Familial hypercholesterolemia (FH) is a monogenic hereditary disorder characterized by impaired lipid metabolism. The prevalence of FH in the general population averages 0.32% (95% CI: 0.26-0.39%). The disease can have both autosomal dominant and autosomal recessive inheritance patterns. Eight FH phenotypes associated with mutations in the LDLRAP1, PCSK9, APOA2, APOB, GHR, GSBS, EPHX2, and LDLR genes are known, which can lead to early manifestation of the pathology. The aim of this review is to comprehensively analyze current literature data on the molecular genetics, biological, and psychological aspects of FH. Analysis of signaling pathways in FH revealed three clusters of genes and their encoded proteins responsible for the following processes: assembly, remodeling, and clearance of plasma lipoproteins (genes: LDLR, LDLRAP1, VLDLR, NPC1L1, APOC1, LPA, CETP, MTTP, APOB, PCSK9); cholesterol metabolism (gene: PPP1R17);regulation of plasma lipoprotein particle levels (gene: ANGPTL3). The proteins PCSK9, APOB, and MTTP were identified as key elements (central hubs) of these metabolic networks. The PPP1R17 protein is involved in the mechanisms of long-term depression, a form of synaptic plasticity. Furthermore, the literature describes an association of FH with five other genes: ABCG5, ABCG8, STAP1, CYP7A1, LIPA, and PNPLA5. Conclusion. Thus, for the early diagnosis and effective management of patients with FH, it is necessary to consider not only the expanded spectrum of associated genes and proteins but also the psychological state of patients, particularly their levels of anxiety, depression, and stress.

Relevance. Oral cancer is one of the most common cancers among neoplasms of the head and neck. Oral cancer is characterized by a poor prognosis, a lack of specific biomarkers and highly effective targeted treatment. Experimental model systems are needed to study oral cancer pathogenesis and develop new treatments. Understanding the molecular features of oral cancer represents one of the key steps in developing new therapeutic strategies. A wide range of biological models is currently available, but their versatility is limited. Experimental models for studying oral cancer have evolved from cell cultures to in vivo systems that mimic pathological processes and the tumor-stroma interactions. Here, we summarized the available information on the current state of experimental oral cancer systems. In vitro models include immortalized and primary cell lines, spheroids and organoids, whereas in vivo models are represented by syngeneic and xenogeneic models, immunocompromised, immunocompetent, humanized, and genetically engineered animals. In vitro models are effective in studying the biology of oral tumors and evaluating the effectiveness of therapy due to high reproducibility and speed of obtaining results. Existing cell lines are widely used for fundamental and translational research and serve as a crucial component in preclinical trials. In vivo models are used in phase II of preclinical research in drug development and thus represent a transitional stage to clinical trials. Conclusion. Despite significant progress in the development of variousexperimental models, each of them has its own advantages and limitations. There is no universal model that allows for the complete extrapolation of the obtained results to the human body. Therefore, when planning research, it is crucial to select carefully the most suitable biological models based on the objectives at hand.

Relevance. One of the objectives of the Anti-Drug Strategy of the Russian Federation until 2030, approved by the Decree of the President of the Russian Federation dated November 23, 2020 № 733, is to improve the drug situation monitoring system, increase the efficiency and objectivity of research in the field of drug control. The document also states that the legal regulation of drug trafficking and anti-drug activities should be carried out taking into account the analysis of the drug situation. Along with monitoring drug use, it is extremely important to study the situation with the use of nicotine-containing substances and alcohol (RF Government Resolution of 20.06.2011 № 485). The study of this problem among the teenage population both in Russia and abroad is of particular relevance for the socio-demographic stability of society. The aim. To conduct a comprehensive monitoring of the drug situation among the adolescent population of the city of Moscow. Materials and Methods. The data for Moscow served as the material for the comprehensive study: medical statistics of the narcological service, the results of an anonymous survey of first-year college students, pilot interviewing of experts - specialists of the Moscow drug addiction service, working in the field of prevention of addictive behavior among children and adolescents. Results and Discussion. A comprehensive study was conducted in the period 2016-2023. A trend of decreasing primary appeals of adolescents for drug addiction treatment was revealed, which is primarily due to a reduction in the group of alcohol consumers, despite this, in general, the situation with adolescent abuse of psychoactive substances remains serious. Conclusion. In connection with the obtained results, it is advisable to conduct further comprehensive monitoring of the drug situation among students (teenagers) and develop, on its basis, proposals for preventive measures among children, teenagers and young people, including in the educational environment.

Relevance. Despite many years of scientific research and clinical results, cancer remains a global health problem. In recent years, there has been an increased interest in studying the role of microorganisms in the occurrence, prognosis and progression of cancer. The probability of isolating carcinogenic microorganisms in the oral microbiota is quite high. In this regard, understanding the role of microorganisms in the occurrence and course of cancer pathology in the future can contribute to the development of innovative strategies for the prevention, treatment of malignant neoplasms and minimization of complications of antitumor treatment. The purpose of this review is a literature analysis of the relationship between representatives of the human oral microbiota in the occurrence and prognosis of cancer. Collection and analysis of 1050 scientific papers using PubMed, Google Scholar and eLIBRARY search engines, published from 2003 to 2024, of which 47 papers are included in this literature review. According to the literature analysis, prevention, diagnostics and treatment of oncological diseases can and should be supplemented by dental approaches aimed at normalizing the microflora. Understanding that oral sanitation significantly reduces its bacterial contamination and, as a result, reduces the number of pathogenic and oncogenic microorganisms can improve the quality of antitumor treatment without significant material and social costs. Conclusion. The use of modern methods of diagnostics and monitoring of oral microbiota in dentistry can become the basis for the development of new strategies for the prevention and treatment of malignant neoplasms of the oral mucosa. Integration of these data into clinical practice requires interdisciplinary cooperation between oncologists, microbiologists and dentists to improve the prognosis of patient treatment.

Relevance. Knowledge of scientific concepts and achievements of the past provides an informative basis for modern research. Moreover, these achievements are filled with the greatest meaning if they are associated with a specific person and the time in which they occurred. Thus, knowledge of the history of science allows us not to neglect the intellectual heritage of past generations and turn it into potential for the development of modern research. In one of his speeches, Nobel laureate Sir Andrew Huxley noted that if he had familiarized himself with the literature of the 19th century in more detail, he would have been able to successfully complete some of his research much faster and more effectively. It must be said that the 19th century gave humanity a whole galaxy of the greatest scientists who made truly fateful discoveries. Our article is dedicated to one of such scientists - Sir Charles Bell (1774-1842), an outstanding Scottish surgeon, anatomist and experimental physiologist. Results of study. In the course of his scientific, teaching and practical medical activities, Bell implemented his accumulated knowledge and experience in the publication of many treatises that remain relevant to this day. Charles Bell applied his talent as an artist in anatomy, personally illustrating magnificent treatises written in collaboration with his older brother, the famous surgeon John Bell, and in surgery (more precisely, in military field surgery), sketching the wounded after the Battle of Waterloo. The scientist also made an invaluable contribution to the development of neurology. Thus, the name of Charles Bell is immortalized in the name of the long thoracic (or «external respiratory») nerve, in the description of lower motor neuron palsy of the facial nerve, and in the «Bell’s sign», when the eyeball rolls upward when trying to close the eye. His description of the differences between the fifth and seventh cranial nerves, as well as the definition of the morpho-functional characteristics of the anterior and posterior roots of the spinal cord as Bell’s law, are widely known. For his invaluable contribution to science, Charles Bell was awarded the gold medal of the Royal Society and made a knight of the Hanoverian Guelphic Order. Conclusion. The statement of the great Russian surgeon N.I. Pirogov, «Everything that is high in the world is art, inspiration and science…» is the most appropriate description of his contemporary Charles Bell, who combined these three hypostases. It is important to note that the reflex theory, whose founder is considered to be Charles Bell, is a fundamental concept of physiology and medicine, although in the early stages (in the mid-19th century) this principle was considered only in relation to the spinal cord.

Relevance. Studies on the development of squamous cell carcinoma of the oral mucosa are of paramount importance due to the widespread of the disease and its aggressive course. When histological examination of the development of squamous cell carcinoma of the oral mucosa is not always possible to determine the first signs of malignancy. Squamous cell carcinoma can develop from epithelial hyperplasia and epithelial dysplasia of varying severity. In addition to histological research methods, immunohistochemical method is widely used for tumor diseases, in which the Ki-67 protein is used, with which the proliferation of epithelial cells can be determined, as well as the P53 protein encoding the TP53 gene, which is a suppressor of tumor growth. It is activated only in the presence of damage to the cell genome. The aim was to evaluate the expression of Ki-67 and P53 proteins in the development of dysplasia and squamous cell carcinoma of the oral mucosa. Materials and Methods. Four groups were identified for the study: group 1-16 patients (34.7%) diagnosed with epithelial hyperplasia, group 2-8 patients (17.3%) diagnosed with low-grade epithelial dysplasia, group 3-9 (19.5%) with a diagnosis of “high-grade epithelial dysplasia”, group 4-13 (28.2%) with a diagnosis of “squamous cell carcinoma”. Mouse monoclonal antibodies to Ki-67 (clone MM1, Diagnostic Biosystems, USA) was used to determine cell proliferation. P53 expression was determined using mouse monoclonal antibodies to the P53 protein (Clone D 07, Novocastra, UK). Monoclonal rabbit antibodies P53 (Clone Y5 Epitomics, USA) were used to study only the “mutant type” of the P53 protein. Results and Discussion. The expression of Ki-67 and P53 proteins were observed in all groups. However, the minimum number of immunopositive cells in the study of P53 (Clone D 07) and P53 (Clone Y5) was observed in the epithelial hyperplasia group, and the maximum in the squamous cell carcinoma group. The increase in the number of stained cells significantly increased as the degree of epithelial dysplasia increased from epithelial hyperplasia and low grade epithelial dysplasia to high grade epithelial dysplasia, etc. Conclusion. Thus, the detection of the expression of the P53 protein (Clone Y5) in the epithelium indicates the presence of changes in the genetic apparatus and metabolism of cells, which can be used in the early diagnosis of squamous cell carcinoma of the oral mucosa.